The overall goal of the proposed research is to achieve a clearer neuroscientific understanding of developmental dyslexia (or reading disability--RD) by means of an integrated program of research across four levels of analysis: 1) genetic, 2) neurological, 3) cognitive, and 4) behavioral. The specific aims and corresponding methodologies for each level of analysis are listed below. Genetic l) To test the hypothesis that there is a quantitative trait locus (QTL) in or near the human lymphocytic antigen (HLA) region of chromosome 6 which both influences RD and alters immune function. This hypothesis will be tested by means of convergent immune and linkage studies. 2) To confirm or disconfirm a linkage between RD and markers on the long arm of chromosome 15 and to screen for other loci on chromosomes besides 6 or 15 that influence RD. This will be accomplished by means of sibling pair linkage studies in two, differently ascertained samples. Neurological 3) To test for genetic and environmental influences on brain structure in RD by performing morphometric analyses of MRI scans collected from RD twin pairs in the Colorado Learning Disability Research Center (CLDRC). Cognitive 4) To test the hypothesis that deficits in phoneme segmentatian are a causal precursor to RD by means of a longitudinal study of young children at high and low family risk for RD. Behavioral 5) To examine the causal basis of the comarbidity between RD and ADHD (and other psychiatric disorders) by doing behavior genetic analyses of psychiatric rating scales and neuropsychological measures of executive function. The measures are being collected from the RD twin sample included in the CLDRC.